This renewal application of the Rochester Alzheimer Disease Project (RADP), focuses its efforts on one of the originally proposed themes of our program: Failed Neuroplasticity-a possible pathophysiological mechanism of Alzheimer's Disease. The present renewal has been retitled as "Neuroplasticity in Aging and Dementia" to more specifically highlight our focus. The RADP seeks to continue its efforts to provide a multidisciplinary Clinical/Neuropathological/Neuroscientific study of Alzheimer's Disease (AD) in order to examine the presence or absence of the plastic response in AD and the potential modulatory factors of this response. The component projects include: CLINICAL CORE- neurologic, psychiatric and general medical assessment will define the disease and its stage; NEUROPATHOLOGY CORE-standard and quantitative examinations will define the presence and degree of Alzheimer change; PROJECT ONE-Quantitative study of dendrites in Aging and Dementia will define the presence or absence of age-related dendritic growth in cortex and hippocampus; PROJECT TWO-Quantitative studies of neuronal loss, glial numbers and Growth Associated Protein in AD and Controls will define the hypothesized stimulus for dendritic growth and associated trophic proteins: PROJECT THREE- Quantitative studies of nucleus basalis and locus coeruleus will define cholinergic and noradrenergic neurons in dementia and aging and their potential contribution to the plastic response; PROJECT FOUR-Quantitative assessment of presynaptic and postsynaptic neuro-chemical pathology in AD and Controls will determine neurochemical plasticity as well as the role of these transmitter systems in dendritic plasticity; PROJECT FIVE- Quantitative studies of NGF message and NGF Receptor message will provide new data on the role of this trophic systems in Aging, Dementia and Neuroplasticity. Viewed as a whole, the three cores and five projects are now tightly focused on one main theme: Failed Neuroplasticity-a possible pathophysiological mechansism in AD. The combined multidisciplinary talents of the group will hopefully contribute a unique and more novel approach to the study of plasticity in aging and dementia.